Synthesis of new heterocyclic isosteres of L-buthionine sulfoximine (L-BSO)

Synthesis of new heterocyclic isosteres of L-buthionine sulfoximine (L-BSO)

P., Thomas; R., Armijo; A., Tapia R.; C., Salas

Abstract:

Glutathione (GSH) in Trypanosoma cruzi, is a pivotal precursor of trypanothione, T(SH)2, the main molecule that protects this parasite of the toxic effects produced by certain drugs, hydrogen peroxide and free radicals. In GSH synthesis, Glutamate Cysteine Ligase (GCL) plays a fundamental role because it catalyzes the limiting step and is inhibited by L-Buthionine Sulfoximine 1 (L-BSO). Recent studies have shown that the reduction in the synthesis of GSH by L-BSO increase the trypanocidal effect of nifurtimox and benznidazol in in vitro models of Chagas’s diseases. In this context, we were interested in developing new heterocyclic isosters of L-BSO. With this purpose we first carried out a 3D model of GCL of T. cruzi, to design new derivatives of L-BSO.

Glutathione (GSH) in Trypanosoma cruzi, is a pivotal precursor of trypanothione, T(SH)2, the main molecule that protects this parasite of the toxic effects produced by certain drugs, hydrogen peroxide and free radicals. In GSH synthesis, Glutamate Cysteine Ligase (GCL) plays a fundamental role because it catalyzes the limiting step and is inhibited by L-Buthionine Sulfoximine 1 (L-BSO). Recent studies have shown that the reduction in the synthesis of GSH by L-BSO increase the trypanocidal effect of nifurtimox and benznidazol in in vitro models of Chagas’s diseases. In this context, we were interested in developing new heterocyclic isosters of L-BSO. With this purpose we first carried out a 3D model of GCL of T. cruzi, to design new derivatives of L-BSO.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013101193156

Referências bibliográficas

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• [4] 4 Lagos, C.; Araya-Secchi, R.; Thomas, P.; Pérez-Acle, T.; Tapia, R. A.; Salas, C. J. Mol.Model. 2012, 18, 2055.

Como citar:

P., Thomas; R., Armijo; A., Tapia R.; C., Salas; "Synthesis of new heterocyclic isosteres of L-buthionine sulfoximine (L-BSO)", p-126-126. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013101193156